Reversion to a homocysteine-responsive phenotype in a human melanoma cell line is associated with diminished growth potential and increased methionine biosynthesis.
Our aim was to determine if the isolation of cells capable of proliferating in methionine-free homocysteine-containing medium, from the human MeWo-LC1 melanoma tumor cell line which is unable to proliferate or survive under such conditions, was associated with altered growth properties. Cells which were able to proliferate in methionine-free homocysteine-containing medium (homocysteine-responsive cells) were obtained from the homocysteine-nonresponsive MeWo-LC1 cell line after 8 months of continuous exposure to methionine-free homocysteine-containing medium. Unlike the parental MeWo-LC1 cell line, these homocysteine-responsive cells were also able to proliferate normally in methionine-free medium containing 5'-deoxy-5'-methylthioadenosine. In vitro growth rate, methionine requirement, and capacity to form colonies on soft agarose of these homocysteine-responsive cells were reduced compared to those of the homocysteine-nonresponsive parental MeWo-LC1 cell line. Unlike MeWo-LC1, these homocysteine-responsive cells were able to synthesize [3H]S-adenosylmethionine from [3H]adenine and homocysteine. The failure of the MeWo-LC1 cell line to proliferate in methionine-free homocysteine-containing medium may be due to a deficiency in the synthesis of methionine from homocysteine and 5-methyltetrahydrofolic acid. These results indicate that acquisition of a homocysteine-responsive phenotype in homocysteine-nonresponsive malignant human tumor cells is associated with a reduction in the autonomous growth potential of such cells.
Liteplo
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RG
Department of Experimental Oncology, Ottawa Regional Cancer Centre, Ontario, Canada.
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D002455:Cell Division; D003470:Culture Media; D003839:Deoxyadenosines; D006710:Homocysteine / Q000494:pharmacology*; D006801:Humans; D008546:Melanoma, Experimental / Q000378:metabolism / Q000473:pathology*; D008715:Methionine / Q000096:biosynthesis*; D010641:Phenotype; D012436:S-Adenosylmethionine; D013763:Tetrahydrofolates / Q000378:metabolism; D013872:Thionucleosides / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D003470:Culture Media; D003839:Deoxyadenosines; D013763:Tetrahydrofolates; D013872:Thionucleosides; D006710:Homocysteine; C008500:5'-methylthioadenosine; D012436:S-Adenosylmethionine; D008715:Methionine; D000241:Adenosine; C005984:5-methyltetrahydrofolate